This Research Plan seeks to provide new information about the effect of degenerative disease, aging, and disorders of neurotransmission on visual fixation and the vertical saccade systems. The information obtained may provide new, diagnostic probes for the detection and quantification of supranuclear disorders of eye movements. In addition, it may add to developing concepts about the pharmacologic treatment of oculomotor disorders. One study investigates the possibility that the selective vunerability of vertical saccades to degenerative disorders, such as Huntingon Disease, is due to a combined discruption of the ascending and descending inputs needed to initiate these vertical movements. Similarly, measurements of vertical saccades may differentiate between Huntingon Disease and nondegenerative choreiform movements disorders. A series of studies continue investigations of the effect of anatomic disorders on visual fixation. For example, choreiform disorders may produce miniature slow drift chorea during fixation. It is also proposed that drug-induced, primary position, downbeat nystagmus is due to an enhancement of the vertical asymmetries of slow drift sporadically observed in normal subjects. An in vivo chronic study of cats tests the omnipause postulate of ocular flutter. If the postulate is true then selectively injuring the omnipause cells with kainic acid may produce spontaneous ocular flutter. A unique study has also presented itself in Northern California. Eight individuals have exposed themselves to a neurotoxin that selectively kills cells in the substantial nigra and produces Parkinson's Disease. This pure hypodopaminergic model in humans can test the effect of dopamine depletion and replacement on the saccade, pursuit, and fixation eye movement systems without the complicating multisystem degeneration commonly found in naturally occurring Parkinson's Symptom Complex. All of these studies have the unifying goal to provide new information about the oculomotor systems that may be of diagnostic or therapeutic value in the clinical setting.